University of East Anglia is pleased to invite applicants to apply for PhD position in chemistry. To be eligible, candidates must be European students. Applicants should apply before May 01, 2015.

Protein ubiquitination represents a post-translational modification that regulates a variety of cellular processes including protein turnover, trafficking, sub-cellular localisation, transcriptional function and DNA repair mechanisms. Ubiquitin conjugation involves a cascade of events catalysed sequentially by E1 (ubiquitin-activating), E2 (ubiquitin-conjugating), and E3 (ubiquitin ligase) enzymes. There are approximately 600 E3 ubiquitin ligases in the mammalian genome, and they are key to providing target substrate specificity. This PhD project will focus on the development of new molecular probes to elucidate the biological roles and substrate-specific function of a small well-defined sub-group known as the HECT E3 ubiquitin ligases. The probes will target multiple sites on ubiquitin ligase domain surfaces using novel bivalent, small-molecules. Of particular interest will be the NEDD4-like E3 ubiquitin-protein ligases WWP1 and WWP2. The latter binds to SMAD proteins in the TGF-ß signalling pathway targeting them for degradation. The TGF-ß family of cytokines controls a variety of normal biological processes, and aberrant TGF-ß activity is associated with major human pathologies including cancer, fibrosis and bone disorders. Here, we aim to use our newly developed molecular probes to understand of how individual E3 ligases impact on these key physiological and pathological events.

Application Requirements

Applicants should have a minimum of a 2.1 degree in Chemistry, Biochemistry, or related disciplines. In most cases UK and EU nationals who have been ordinarily resident in the UK for 3 years prior to the start of the course are eligible for a full-award. Other EU nationals may qualify for a fees only award. All candidates should check to confirm their eligibility for funding.